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Nanomaterials 2018, 8(2), 64; https://doi.org/10.3390/nano8020064

Three-Dimensional Hepatocellular Carcinoma/Fibroblast Model on a Nanofibrous Membrane Mimics Tumor Cell Phenotypic Changes and Anticancer Drug Resistance

1
Department of Advanced Convergence Technology, Korea Polytechnic Univsersity, Siheung-si 15073, Gyoenggi-do, Korea
2
Department of Mechanical System Engineering, Korea Polytechnic Univsersity, Siheung-si 15073, Gyoenggi-do, Korea
3
Department of Mechanical Engineering, Korea Polytechnic Univsersity, Siheung-si 15073, Gyoenggi-do, Korea
4
School of Mechanical Engineering, Kyungpook National University, Buk-gu, Daegu 702-701, Korea
5
Department of Pharmacology, Ajou University School of Medicine, Suwon 442-721, Korea
6
Department of Anatomy, Pusan National University School of Medicine, Yangsan 626-770, Korea
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Received: 5 December 2017 / Revised: 22 January 2018 / Accepted: 23 January 2018 / Published: 25 January 2018
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Abstract

Three-dimensional (3D) in vitro tissue or organ models can effectively mimic the complex microenvironment of many types of human tissues for medical applications. Unfortunately, development of 3D cancer models, which involve cancer/stromal cells in a 3D environment, has remained elusive due to the extreme complexity of the tumor microenvironment (TME) and the stepwise progression of human cancer. Here, we developed hepatocellular carcinoma (HCC) models, which consist of fibroblasts as stromal cells, HCC cells, and a nanofibrous membrane to mimic the complex TME. The 3D HCC models were fabricated using three distinct culture methods: cancer cells grown directly on the nanofibrous membrane (mono model), fibroblasts covering the nanofibrous membrane (layer model), and both cancer cells and fibroblasts grown on the nanofibrous membrane (mixed model). Interestingly, the mono model and layer model showed similar tissue structures, whereas the mixed model resulted in phenotypic changes to the cancer cells. Further analysis demonstrated that the mixed models promoted the expression of fibronectin and vimentin, and showed higher resistance to anticancer drugs compared with the other models. Thus, our 3D HCC model could be utilized for testing efficient anticancer therapies at various stages of cancer, with potential application to different tumor types. View Full-Text
Keywords: tumor microenvironment; hepatocellular carcinoma; nanofibrous membrane tumor microenvironment; hepatocellular carcinoma; nanofibrous membrane
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Le, B.D.; Kang, D.; Yun, S.; Jeong, Y.H.; Kwak, J.-Y.; Yoon, S.; Jin, S. Three-Dimensional Hepatocellular Carcinoma/Fibroblast Model on a Nanofibrous Membrane Mimics Tumor Cell Phenotypic Changes and Anticancer Drug Resistance. Nanomaterials 2018, 8, 64.

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